Synthesis Component - Wooley Group The primary activities conducted in the Wooley laboratory have focused upon shell crosslinked knedellike (SCK) nanoparticles as the nanoscale framework. Efforts have included the development of a scaled-up synthesis of well-defined SCKs having required biodistribution performance to be used as a large batch for multiple in vitro and in vivo studies, the development of chemistries to label the SCKs efficiently and selectively with imaging agents and targeting ligands, the introduction of degradable/multifunctional crosslinkers to be used in the construction of the SCKs, and the implementation of a new strategy to provide aqueous-only pH-induced block copolymer assembly for the construction of SCKs, while also allowing for iodine labeling within their cores. Experiments have also been initiated to develop novel nanostructures based upon hyperbranched copolymers of ethylene oxide and fluorocarbon units. Six specific goals and the progress made toward them are listed below. Goal 1: Preparation of large batches of SCKs having PS as the core for general applications in the numerous labeling/loading schemes for imaging and animal studies. Goal 2: Labeling of DOTA-SCK/Micelle conjugates with Gd for MRI Goal 3: Conjugation of cyclic peptidc KCRGDC to SCKs/Micelles for binding affinity studies with respect to avp3 and avp5 Goal 4: Development of new chemistries for the attachment of ligands to SCKs and hydrolyticallydegradable SCKs Goal 5: Development of aqueous-only pH-induced nanoobject assembly and core-iodine labeling Goal 6: Emerging new nanostructures based on hyperbranched fluoropolymer (HBFP)(C) Imaging Sciences Component[unreadable] The primary goals of the Imaging Component of the NHLBI-PEN "Integrated Nanosystems for Diagnosis and Therapy" are 1) to label the developed nanostructures with large numbers of detectable elements, thus providing imaging tools with increased sensitivity, and 2) to evaluate these structures (both targeted and nontargeted) in normal animals and disease models. In particular, the direct comparison of the targeted particlebased tracers to the non-conjugated targeting moieties in the diseased animals will allow us to prove the benefits deriving form the use of nanomaterials for medical applications.